1. Aspartic Acid
Aspartic acid is an amino acid having the formula HOOC—CH2—CH(NH2)—COOH. Its conjugate base (formed by losing a proton) is known as aspartate. For example, sodium aspartate NaOOC—CH2—CH(NH2)—COOH is the sodium salt of aspartic acid. Aspartic acid and aspartate are biologically equivalent in most respects and the term “aspartic acid” is used herein to refer to both compounds.
Closely related derivatives of aspartic acid are also known. One class of derivatives, known as esters, are formed by substituting an —OR′ group (where R′ represents an alkyl or an aryl group) for the —OH in one of the carboxylic groups (—COOH). For example, methyl aspartate CH3OOC—CH2—CH(NH2)—COOH is an ester. Another type of derivative is formed by substituting a methyl group (—CH3) for one of the hydrogens of the amino group (—NH2). For example, N-methyl-aspartate is a derivative having the formula HOOC—CH2—CH(NHCH3)—COOH. Aspartic acid, its salts such as sodium aspartate, its esters such as methyl aspartate, and other derivatives such as N-methyl-aspartate are nearly biologically equivalent in some respects and the term “aspartic acid compound” is used herein to refer to them.
In aspartic acid, the carbon atom attached to the amino group is asymmetric, i.e., it has four different groups attached to it. The presence of an asymmetric carbon makes aspartic acid a member of the class of compounds that exists in one of two optically active forms. The two forms, known as enantiomers, are mirror images of each other. They differ only in the orientation of the four groups that are attached to the asymmetric carbon.
Enantiomers have identical chemical properties except toward optically active reagents. Optically active reagents are very common in biological systems. As a result, enantiomers often have very different functions in the body.
Enantiomers are sometimes analogized to a right hand and a left hand. The two hands are mirror images of each other and are identical in most respects. However, they differ dramatically in how they fit within a right-handed glove.
One of the two enantiomers of aspartic acid is known as levorotatory aspartic acid or by the abbreviations (−)-aspartic acid, (l)-aspartic acid, or L-aspartic acid. The other enantiomer of aspartic acid is known as dextrorotary aspartic acid or by the abbreviations (+)-aspartic acid, (d)-aspartic acid, or D-aspartic acid. A mixture of equal parts of both enantiomers is known as a racemic mixture, a racemic modification, or a racemate and is designated as (±)-aspartic acid or DL-aspartic acid. The terms L-aspartic acid and D-aspartic acid are used herein for the enantiomers and DL-aspartic acid is used for the racemic mixture.
L-aspartic acid is one of the twenty-six amino acids that make up proteins. L-aspartic acid is a common nutritional supplement.
D-aspartic acid is also present in the human body, but in much smaller amounts than L-aspartic acid. As discussed in the following sections, D-aspartic acid is believed to play a role in the generation of certain hormones in male humans.
2. Male Hormones
Hormones are molecules that carry signals from one group of cells to another group of cells. Three such hormones are testosterone, growth hormone (GH), and insulin-like growth factor 1 (IGF-1).
Testosterone is the major male sex hormone in humans and other mammals. It is produced primarily in the testes. Testosterone is responsible for a wide range of beneficial effects, including increases in muscle mass, strength, and sexual performance. Growth hormone is produced in the pituitary gland and is also responsible for a wide range of beneficial effects, including increases in muscle mass. Insulin-like growth hormone 1 is produced in the liver and is further responsible for a wide range of beneficial effects.
These three hormones are at their highest levels during young adulthood when physical condition (including athletic and sexual performance) is greatest. The levels typically decline gradually as men age. Many of the undesirable effects of aging are believed to be caused by the declining levels of hormones. It is believed that increasing the levels of these three hormones improves the physical condition of adult males of all ages. However, increasing the levels by simply adding the hormones carries with it certain disadvantages.
3. The Production Of Male Hormones
The production of testosterone, growth hormone (GH), and insulin-like growth factor 1 (IGF-1) hormones in male mammals is regulated by a complex and not fully understood communication system between the hypothalamus gland located at the base of the brain, the pituitary gland (another gland located at the base of the brain), the liver, and the testes.
In the case of testosterone, its production is believed to be at least partially controlled by the following system and pathways in male humans. The hypothalamus has receptors that detect the level of testosterone in the blood. When the level becomes low, the hypothalamus generates a gonadotropin releasing hormone (GnRH) that is detected by the pituitary gland. In response to the GnRH hormone, the pituitary gland generates a luteinizing hormone (LH) that is detected by the testes. In response to the LH hormone, the testes produce testosterone.
The production of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are apparently regulated by similar systems and pathways. The hypothalamus generates a growth hormone releasing hormone (GHRH) that triggers the release of growth hormone (GH) by the pituitary. GHRH is released in pulsatile fashion and the subsequent release of GH from the pituitary is also pulsatile in nature. GH stimulates the liver to increase production and release of IGF-1. Increased levels of IGF-1 promote production of somatostatin, also known as growth hormone inhibiting hormone (GH1H), in the hypothalamus. Somatostatin acts on the hypothalamus and pituitary to decrease production of GHRH and GH. This regulatory system of GHRH, GH, IGF-1, and somatostatin is referred to as the GH/IGF-1 axis.
4. Animal Studies With D-Aspartic Acid
As previously mentioned, levels of testosterone, growth hormone, and insulin-like growth factor 1 in the blood can be increased by simply administering the hormones themselves. The levels can also be increased by adding other hormones (such as gonadotropin releasing hormone or luteinizing hormone) or prohormones that trigger the body to produce the three hormones. The addition of hormones carries the potential for serious side effects and many hormones are available only with a physician's prescription.
Some recent research has indicated that certain non-hormonal compounds may also have an effect on the production of hormones in male mammals. Many experiments have been performed involving the administration of D-aspartic acid or N-methyl-D-aspartate to animals of species ranging from rats to sheep to lower primates. The administration of these two compounds has been performed by injection into the bloodstream. N-methyl-D-aspartate has also been administered orally.
For example, the administration of D-aspartic acid and N-methyl-D-aspartate has been shown to cause an increase in testosterone and growth hormone levels in the animals. Antimo D'Aniello, “D-Aspartic Acid: An Endogenous Amino Acid With An Important Neuroendocrine Role,” Brain Research Reviews, Vol. 53, No. 2, pp. 215-234 (2007); and R. Boni et al., “Puberty In Monkeys Is Triggered By Chemical Stimulation Of The Hypothalamus,” Proceedings of the National Academy of Sciences, Vol. 86, No. 7, pp. 2506-2510 (1989). The administration of N-methyl-D-aspartate has been shown to cause an increase in growth rate. G. Xi et al., “Growth Associated Hormones Response And Fat Metabolism Change In Finishing Pigs Fed With N-Methyl-D-Aspartate,” Asian-Australian Journal of Animal Science, Vol. 15, No. 7, pp. 1026-1030 (2002).
As additional examples, the administration of D-aspartic acid has been shown to stimulate the release of luteinizing hormone from the pituitary, both in-vitro and in-vivo. T. Fukushima et al., “Studies On The Fate of D-Aspartic Acid In Pineal And Pituitary Glands Of Rats And Intravenous Administration,” Proc. Japan. Acad, Vol. 74, No. B, pp. 18-23 (1998). The administration of D-aspartic acid has been shown to stimulate the release of testosterone from the testes, both in-vitro and in-vivo. Antimo D'Aniello, “Involvement Of D-Aspartic Acid In The Synthesis Of Testosterone In Rat Testes,” Life Sciences, Vol. 59, No. 2, pp. 97-104 (1996). The administration of D-aspartic acid or N-methyl-D-aspartate has been shown to stimulate growth hormone production from the pituitary gland both in-vitro and in-vivo. Antimo D'Aniello et al., “Occurrence Of D-Aspartic Acid and N-Methyl-D-Aspartic Acid In Rat Neuroendocrine Tissues And Their Role In The Modulation Of Luteinizing Hormone And Growth Hormone Release,” The FASEB Journal, Vol. 14, pp. 699-714 (2000).
5. Human Studies With D-Aspartic Acid
No studies have examined the effects of D-aspartic acid or N-methyl-D-aspartate on male humans. It is well known that different species of mammals often have different responses to hormones. Therefore, it is unknown whether, and to what degree, the administration of D-aspartic acid compounds in different ways and at different levels to male humans causes an increase in levels of testosterone, growth hormone, and insulin-like growth factor 1.
Accordingly, there is a demand for a method of improving the physical condition of adult male humans of all ages by increasing their levels of testosterone, growth hormone, and insulin-like growth factor 1 without the administration of hormones or prohormones.